EP0222145B1 - Process for the preparation of carboxylic acids and their alkali metal salts - Google Patents

Description

The present invention relates to a new process for the preparation of carboxylic acids or their alkaline salts, which invention is based on a fortuitous discovery on our part. We have indeed observed that certain alkali metal alcoholates, in particular potassium, reacted, in solution in an inert organic solvent, with carbon monoxide to provide the corresponding carboxylates. It is schematically the reaction which follows:

Une telle réaction avait été décrite par Geuther et Frôtich [voir Liebigs Ann. Chem. 202, 288 (1880)] qui toutefois avaient limité leurs études à des alcoolates dérivés d'alcools aliphatiques simples, linéaires et saturés, le méthylate et l'éthylate de sodium en particulier. D'autre part, au vu de la méthodologie suivie, les rendements observés étaient bas et le procédé s'est révélé peu aisé dans son application industrielle : l'alcoolate alcalin était en effet fondu et traité avec du CO. Ceci peut expliquer la raison pour la- qauelle cette réaction n'a pas été reprise par la suite et les travaux de Geuther et Frôlich sont tombés dans l'oubli.

Such a reaction had been described by Geuther and Frôtich [see Liebigs Ann. Chem. 202, 288 (1880)] who, however, had limited their studies to alcoholates derived from simple, linear and saturated aliphatic alcohols, sodium methylate and ethylate in particular. On the other hand, in view of the methodology followed, the yields observed were low and the process proved to be difficult in its industrial application: the alkaline alcoholate was in fact melted and treated with CO. This may explain the reason why this reaction was not resumed later and the work of Geuther and Frôlich fell into oblivion.

However, there is a definite interest in the preparation of carboxylic acids carrying an unsaturation of the allylic type; such compounds are in fact difficult to access by means of the commonly used synthesis methods.

The present invention provides a new and industrially practicable solution to this problem.

The process according to the invention is intended for the preparation of carboxylic acids and their alkaline salts of formula (I) in which X defines a hydrogen, or an alkali metal atom, and R ¹ and R ^{2, which are} identical or different, represent each a linear or branched, saturated or unsaturated alkyl residue, which process is characterized in that

A. treats an alcoholate of formula (II) in which Me represents an alkali metal atom, in solution in an inert organic solvent, under the reaction conditions, with CO at a pressure between 35 and 450 bar and at a temperature between 120 and 160 ° C, then treats the alkaline carboxylate obtained with water and finally acidifies the resulting aqueous solution to provide the desired acid, or

B. treats with CO an alcoholate of formula (II) dissolved in an inert organic solvent under the conditions of the reaction in the presence of a ligand reagent for alkaline cations, at a pressure between 40 and 80 bar and at a temperature from 15 to 45 _° C, then treats the alkaline carboxylate obtained with water and finally acidifies the resulting aqueous solution to provide the desired acid.

In formula (1), R ¹ and R ² can represent various alkyl radicals. They can thus define a linear saturated lower Ci-Ce alkyl as well as an alkyl radical comprising one or more unsaturations. By way of example, mention may be made of methyl, ethyl, n-propyl, isopropyl, n-butyl, iso-butyl, tert-butyl, n-pentyl or unsaturated radicals such as vinyl, crotonyl or else - (CH ₂ ) ₂ -CH = C (CH ₃ ) ₂ .

By way of example, mention should be made, as starting materials, of the alcoholates derived from linalool and from 3-vinyl-1-octene-3-ol, of formula (III) and (IV) respectively.

The alcoholates are easily obtained by the usual methods from the corresponding alcohol. As the preferred alcoholate, potassium alcoholate is used, which is prepared by treating the alcohol with potassium hydride. It is preferably carried out in an inert organic solvent, for example an aromatic hydrocarbon such as benzene. In such a solvent, the potassium alcoholate is generally soluble and the resulting solution can be directly treated with CO in accordance with the process of the invention. This operation takes place as indicated above at a pressure above atmospheric pressure and a conventional autoclave made of stainless steel is used for this purpose.

According to variant B. of the process of the invention, the reaction takes place in the presence of a ligand reagent for alkaline cations. Such reagents are known as crown ethers. Most of these are commercial products, the nature of which depends on the specific use considered. As a preferred ligand reagent for the K ⁺ cation, it has been found that the product known under the name 18-crown-6 [see EV Dehmlow and SS Dehmlow, Phase Transfer Catalysis, Verlag Chemie (1983), p. 19] fits perfectly.

For the isolation of the reaction products, the procedure is as follows: the excess potassium hydride is first destroyed using isopropanol and the resulting mixture is poured into water. The aqueous phase containing the alkaline salt is then acidified and extracted using organic solvents. The acids are thus obtained directly by evaporation of the organic phase. According to variant B., the aqueous phase is saturated with KCI in order to keep the crown ether in the aqueous solution itself.

We have observed that the reaction which characterizes the process of the present invention proceeds with complete retention of the configuration. This is how by using an alcohol optically active late with defined isomeric structure, the corresponding acid of the same isomeric configuration is obtained.

The invention is illustrated in more detail in the examples which follow in which the temperatures are indicated in degrees centigrade and the abbreviations have the usual meaning.

Example 1 2,6-dimethyl-2-vinyl-5-hentenoic acid

3.52 grams of KH dispersed in a mineral oil (Aldrich, 35% KH, 30.7 mM) were washed several times with pentane and the oil is removed by decantation. The resulting KH was suspended in 30 ml of anhydrous benzene. To the resulting cooled suspension, 3 g (19 mM) of linalool in 10 ml of benzene were added over 5 minutes with stirring. The addition is accompanied by release of hydrogen and the mixture was stirred for 2 h at room temperature. These operations were carried out under argon in a glass container whose shape matches that of the autoclave, the container having been closed using a rubber capsule. The whole was then introduced into the autoclave and the container was opened, then at ambient temperature, CO was introduced (purity 99.97%) until a pressure of 360 bar was obtained. The autoclave was then closed and heated in 40 min. at 130 _° , the CO pressure thus reaches 430 bar, then it was stirred at 130 _° for 15 h. After cooling, the excess gas was removed and the autoclave was opened. The contents of the glass container were treated with a few drops of water or isopropanol to remove excess KH and the resulting mixture was poured into water (50 ml) and diethyl ether. The mixture was then extracted with ether.

The remaining alkaline aqueous phase was acidified with aqueous HCl, saturated with NaCl and extracted with ether. The ethereal extracts thus obtained were dried and concentrated to provide 2 g of the desired acid.

Example 2 2,6-dimethy-2-vinvl-5-heptenoic acid

The potassium alcoholate of (S) - (+) - linalool was prepared from an alcohol having an enantiomeric purity of 62 ± 5% (1.54 g) and 1.73 g of KH dispersed in a mineral oil (see Example 1 above). The resulting benzene solution was treated with 4.75 g of 18-crown-6 (18-crown-6; Aldrich, 18 mM) and the resulting mixture was stirred for 1 h. This resulted in a solution which was introduced, as indicated in Example 1, into an autoclave and CO was introduced until a pressure of 50 bar was obtained. At this pressure, the autoclave was closed, magnetically stirred and heated to 40 _° for 113 h. The pressure thus reaches 55 bar. After cooling, the reaction mixture was treated as indicated in the previous example. The acid fraction was distilled using a ball oven (bath temperature 100-250 _° / 0.66 Pa) to provide 0.471 g of a mixture containing 55.8% of the desired acid: [alpha] ² 20 = + 2.11 ± 0.12 _° (c = 0.760 g / 100 ml CHCI ₃ ). By esterification using a reaction with diazomethane, it was possible to obtain the corresponding methyl ester having [alpha] ² 20 D = + 2.05 ± 0.08 ° (c = 1.290 g / 100 ml CHCIs) , enantiomeric purity 55 ± 5%. Methyl 2,6-dimethyl-2-vinyl-5-heptenoate presents an interesting olfactory note of floral, fresh type.

Example 3 2-vinyl-2-pentyl-3-butenoic acid

1.00 gram of 3-vinyl-1-octene-3-ol (purity 81%) was transformed into the corresponding potassium alcoholate as indicated in Example 1 and subjected to reaction with CO according to the same procedure as that followed for linalool (CO pressure: 45 bar; temperature: 120 _° , reaction time: 12 h). The desired acid was obtained as a mixture, the acid content of which was about 55%.

By carrying out the reaction in the presence of 18-crown-6 ether, as described in Example 2 (CO pressure: 360 bar; ambient temperature; reaction time: 65 h), the desired acid was obtained in the form of 'a mixture with an acid content of 60.6%.

By esterification with diazomethane, it was possible to isolate the corresponding methyl ester, or methyl 2-vinyl-2-penyl-3-butenoate. NMR (360 MHz): 0.88 (3H, t); 1.20-1.37 (6H, m); 2.76-2.85 (2H, m); 3.72 (3H, s); 5.12 (2H, d); 5.23 (2H, d); 6.04 (2H, dxd) delta ppm; MS: M ⁺ = 196; m / e: 139 (28), 126 (27), 125 (23), 95 (36), 94 (26), 81 (67), 79 (34), 67 (100). ANNEX

Claims (7)

1. Process for the preparation of carboxylic acids or alkali salt derivatives thereof of formula (I)

wherein X stands for a hydrogen or an alkali metal atom, and R¹ and R² are identical or different and represent each a linear or branched, saturated or unsaturated alkyl radical, characterized in that:

A. an alkoxide formula (11)

wherein Me stands for an alkali metal atom, in solution in an inert organic solvent under the reaction conditions, is treated with CO at a pressure of between 35 and 450 bar and at a temperature of between 120 and 160_°C, the thus obtained alkaline carboxylate is then treated with water and the resulting aqueous solution is finally acidified to give the desired acid, or B. an alkoxide of formula (II), in solution in an inert organic solvent under the reaction conditions, in the presence of a ligand of alkali metal cations, is treated with CO at a pressure of between 40 and 80 bar and at a temperature of 15 to 45_°C, the thus obtained alkali carboxylate is then treated with water and the resulting aqueous solution is finally acidified to give the desired acid.

2. Process according to claim 1, characterized in that one uses as aikoxide of formula (II) the compound of formula (V)

wherein Me stands for an alkali metal atom, and in that 2,6-dimethyl-2-vinyl-5-heptenoic acid or one of its corresponding alkali metal salts is obtained.

3. Process according to claim 1, characterized in that one uses as alkoxide of formula (II) the compound of formula (VI)

wherein Me represents an alkali metal atom, and in that 2-vinyl-2-pentyl-3-butenoic acid or one of its corresponding alkali metal salts is obtained.

4. Process according to claim 1, characterized in that a potassium alkoxide is used as alkoxide of formula (II).

5. Process according to claim 1, characterized in that the ligand of alkali metal cations is chosen amongst the crown ethers.

6. Process according to claim 5, characterized in that the crown ether is the 18-crown-6.